Robust dose planning objectives for mesorectal radiotherapy of early stage rectal cancer – A multicentre dose planning study

Background and purpose Organ preservation strategies are increasingly being explored for early rectal cancer. This requires revision of target volumes according to disease stage, as well as new guidelines for treatment planning. We conducted an international, multicentre dose planning study to develop robust planning objectives for modern radiotherapy of a novel mesorectal-only target volume, as implemented in the STAR-TReC trial (NCT02945566). Materials and methods The published literature was used to establish relevant dose levels for organ at risk (OAR) plan optimisation. Ten representative patients with early rectal cancer were identified. Treatment scans had mesorectal target volumes as well as bowel cavity, bladder and femoral heads outlined, and were circulated amongst the three participating institutions. Each institution produced plans for short course (SCRT, 5 × 5 Gy) and long course (LCRT, 25 × 2 Gy) treatment, using volumetric modulated arc therapy on different dose planning systems. Optimisation objectives for OARs were established by determining dose metric objectives achievable for ≥90% of plans. Results Sixty plans, all fulfilling target coverage criteria, were produced. The planning results and literature review suggested optimisation objectives for SCRT: V10Gy < 180 cm3, V18Gy < 110 cm3, V23Gy < 85 cm3 for bowel cavity; V21Gy < 15% and V25Gy < 5% for bladder; and V12.5Gy < 11% for femoral heads. Corresponding objectives for LCRT: V20Gy < 180 cm3, V30Gy < 130 cm3, V45Gy < 90 cm3 for bowel cavity; V35Gy < 22% and V50Gy < 7% for bladder; and V25Gy < 15% for femoral heads. Constraints were validated across all three institutions. Conclusion We utilized a multicentre planning study approach to develop robust planning objectives for mesorectal radiotherapy for early rectal cancer

BMI Development of Normal Weight and Overweight Children in the PIAMA Study

Background: There is evidence that rapid weight gain during the first year of life is associated with overweight later in life. However, results from studies exploring other critical periods for the development of overweight are inconsistent. Objective: The objective was to investigate BMI development to assess at what ages essential differences between normal weight and overweight children occur, and to assess which age intervals the most strongly influence the risk of overweight at 8 years of age. Methods: Longitudinal weight and height data

Non-participation in population-based disease prevention programs in general practice

<p>Abstract</p> <p>Background</p> <p>The number of people with a chronic disease will strongly increase in the next decades. Therefore, prevention of disease becomes increasingly important. The aim of this systematic review was to identify factors that negatively influence participation in population-based disease prevention programs in General Practice and to establish whether the program type is related to non-participation levels.</p> <p>Methods</p> <p>We conducted a systematic review in Pubmed, EMBASE, CINAHL and PsycINFO, covering 2000 through July 6th 2012, to identify publications including information about characteristics of non-participants or reasons for non-participation in population-based disease prevention programs in General Practice.</p> <p>Results</p> <p>A total of 24 original studies met our criteria, seven of which focused on vaccination, eleven on screening aimed at early detection of disease, and six on screening aimed at identifying high risk of a disease, targeting a variety of diseases and conditions. Lack of personal relevance of the program, younger age, higher social deprivation and former non-participation were related to actual non-participation. No differences were found in non-participation levels or factors related to non-participation between the three program types. The large variation in non-participation levels within the program types may be partly due to differences in recruitment strategies, with more active, personalized strategies resulting in higher participation levels compared to an invitation letter.</p> <p>Conclusions</p> <p>There is still much to be gained by tailoring strategies to improve participation in those who are less likely to do so, namely younger individuals, those living in a deprived area and former non-participants. Participation may increase by applying more active recruitment strategies.</p

Cellular dissection of psoriasis for transcriptome analyses and the post-GWAS era

Abstract Background Genome-scale studies of psoriasis have been used to identify genes of potential relevance to disease mechanisms. For many identified genes, however, the cell type mediating disease activity is uncertain, which has limited our ability to design gene functional studies based on genomic findings. Methods We identified differentially expressed genes (DEGs) with altered expression in psoriasis lesions (n = 216 patients), as well as candidate genes near susceptibility loci from psoriasis GWAS studies. These gene sets were characterized based upon their expression across 10 cell types present in psoriasis lesions. Susceptibility-associated variation at intergenic (non-coding) loci was evaluated to identify sites of allele-specific transcription factor binding. Results Half of DEGs showed highest expression in skin cells, although the dominant cell type differed between psoriasis-increased DEGs (keratinocytes, 35%) and psoriasis-decreased DEGs (fibroblasts, 33%). In contrast, psoriasis GWAS candidates tended to have highest expression in immune cells (71%), with a significant fraction showing maximal expression in neutrophils (24%, P < 0.001). By identifying candidate cell types for genes near susceptibility loci, we could identify and prioritize SNPs at which susceptibility variants are predicted to influence transcription factor binding. This led to the identification of potentially causal (non-coding) SNPs for which susceptibility variants influence binding of AP-1, NF-κB, IRF1, STAT3 and STAT4. Conclusions These findings underscore the role of innate immunity in psoriasis and highlight neutrophils as a cell type linked with pathogenetic mechanisms. Assignment of candidate cell types to genes emerging from GWAS studies provides a first step towards functional analysis, and we have proposed an approach for generating hypotheses to explain GWAS hits at intergenic loci.http://deepblue.lib.umich.edu/bitstream/2027.42/109537/1/12920_2013_Article_485.pd